Etv3 in dendritic cells is key for maintaining immune balance; its absence causes Treg cell expansion and T cell activation issues. 🧬 PMID:41678619, Science 2026, @ScienceMagazine https://doi.org/10.1126/science.ads1246 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Phase 1 trial shows potential for rezatapopt, a p53 reactivator, in treating TP53 Y220C-mutated tumors over a 21-day cycle. Exciting prospects! PMID:41740031, N Engl J Med 2026, @NEJM https://doi.org/10.1056/NEJMoa2508820 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

A study in JAMA Neurology finds high EBV-derived EBNA-1 antibody titers could help distinguish MS from MOGAD and NMOSD. PMID:41801194, JAMA Neurol 2026, @JAMANeuro https://doi.org/10.1001/jamaneurol.2026.0240 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Identification of an allosteric site on the E3 ligase adapter cereblon | Nature Cereblon (CRBN) is the target of thalidomide derivatives1 that achieve therapeutic efficacy against some haematologic neoplasias2–4 by recruiting neosubstrates for degradation5–7. Despite the intense investigation of orthosteric thalidomide derivatives, little is known about alternate binding sites on CRBN. Here we report an evolutionarily conserved cryptic allosteric binding site on CRBN. Small-molecule SB-405483 binds the allosteric site to cooperatively enhance the binding of orthosteric ligands and alter their neosubstrate degradation profiles. A survey of over 100 orthosteric ligands and their degradation targets reveals trends in the classes of compounds and neosubstrates in which degradation outcomes are enhanced or inhibited by SB-405483. Structural investigations provide a mechanistic basis for the effects of the allosteric ligand by shifting the conformational distribution of CRBNopen to a novel CRBNint and increasing the CRBNclosed state. The discovery of a cryptic allosteri

Discovery: Cereblon has a conserved allosteric site. SB-405483 binds there, boosting function. Key for new therapeutic strategies beyond thalidomide derivatives. PMID:41565821, Nature 2026, @Nature https://doi.org/10.1038/s41586-025-09994-w #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Study predicts which adolescents benefit from school mindfulness via baseline traits; crucial step as depression starts young. PMID:41706471, JAMA Psychiatry 2026, @JAMAPsych https://doi.org/10.1001/jamapsychiatry.2025.4638 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

A pilot RCT at Univ. of Pittsburgh studied low-dose lithium7 for MCI. It assessed cognition & biomarkers. Feasible & safe! PMID:41770546, JAMA Neurol 2026, @JAMANeuro https://doi.org/10.1001/jamaneurol.2026.0072 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

New policies can boost diagnostic innovation. Investments could address 90% of global disease burden, impacting millions worldwide. PMID:41955384, Science 2026, @ScienceMagazine https://doi.org/10.1126/science.aec0173 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Setidegrasib (ASP3082) tested for KRAS G12D involvement: targets NSCLC (5%) & pancreatic cancer (40%). Phase 1 study examined safety & efficacy. PMID:41879829, N Engl J Med 2026, @NEJM https://doi.org/10.1056/NEJMoa2600752 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Genome-wide study of 1,434 Japanese MG cases reveals TERT locus (OR=1.31, P=1.7x10^-10) as key. This insight could reshape MG treatment strategies. PMID:41820352, Nat Commun 2026, @NatureComms https://doi.org/10.1038/s41467-026-70376-5 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Discover the mitochondrial transfer network between Leydig cells and testicular macrophages crucial for testosterone synthesis!🔥💡 PMID:41760931, Nat Cell Biol 2026, @NatureCellBio https://doi.org/10.1038/s41556-026-01896-x #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Tumor acidosis induces a CS-enriched glycocalyx, enhancing lipid scavenging and resisting ferroptosis. Exciting insights! PMID:41673170, Nat Cell Biol 2026, @NatureCellBio https://doi.org/10.1038/s41556-026-01879-y #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

A JAMA Psychiatry review links climate-related, nature-based interventions to improved mental health outcomes, analyzing SRMAs. PMID:41779404, JAMA Psychiatry 2026, @JAMAPsych https://doi.org/10.1001/jamapsychiatry.2026.0037 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

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Air pollution & extreme temps harm kidneys! 🚨 Studies reveal PM₂.₅ & PM₁₀ pollutant dangers, tapping into ignored health realms. 🌍💧 PMID:41957144, Nat Rev Nephrol 2026, @NatRevNeph https://doi.org/10.1038/s41581-026-01073-1 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Metabolic masqueraders of paediatric and adult rheumatic diseases | Nature Reviews Rheumatology Inborn errors of metabolism comprise a clinically diverse group of conditions that arise from the decreased activity of an enzyme or metabolite transporter and subsequent blockade in a metabolic pathway. These disorders are typically considered in the differential diagnosis of critically ill neonates or young children presenting with hypoglycaemia, metabolic acidosis or hyperammonaemia. However, beyond these classic presentations, a broader group of inborn errors of metabolism can manifest more subtly, with progressive articular and multi-systemic involvement that mimics or overlaps with typical features of rheumatological disease. Consequently, these conditions might be misdiagnosed for years as rheumatological diseases, including juvenile idiopathic arthritis, systemic sclerosis, idiopathic inflammatory myopathies and systemic lupus erythematosus. Moreover, these disorders provide unique opportunities to understand the complex interplay between metabolism and immune function. With th

Metabolic disorders often mimic rheumatic diseases in children & adults, beyond neonatal issues like hypoglycaemia. PMID:41741762, Nat Rev Rheumatol 2026, @NatRevRheumatol https://doi.org/10.1038/s41584-026-01352-y #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Mutant IDH1-R132H undergoes autopalmitoylation at C269, enhancing its cancer-driving activity by producing (R)-2HG metabolite. PMID:41530531, Nat Chem Biol 2026, @nchembio https://doi.org/10.1038/s41589-025-02131-8 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Atypical protein kinase C activation drives intestinal glucose excretion in diabetes mellitus | Nature Communications Intestinal glucose excretion, defined as increased intestinal serum glucose uptake and secretion into the lumen, influences bariatric surgery-associated glycaemic control. Here, we investigate molecular mechanisms that activate intestinal glucose excretion. We evaluate altered transcriptomes in variable intestinal glucose excretion models and big data-based drug discovery systems. We show that protein kinase C (PKC) activation mimics transcriptome alterations observed during intestinal glucose excretion. Among PKC subfamilies, atypical PKC (aPKC) facilitates glucose transporter 1 (GLUT1)-mediated intestinal glucose excretion without inducing oncogenic proliferation. Intestinal aPKC activation via transposon expression vector induces serum glucose uptake into intestinal tissues and excretion into the lumen. Prostratin, a non-tumorigenic phorbol ester, activates aPKC and induces a similar effect on intestinal glucose excretion. We identify the prostratin and aPKC/GLUT1 signalling pathway

PKC activation in diabetes drives intestinal glucose excretion, revealing a potential pathway for glycaemic control interventions post-bariatric surgery. PMID:41651859, Nat Commun 2026, @NatureComms https://doi.org/10.1038/s41467-026-69193-7 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Efficiency in clearing amyloid-β (Aβ) in Alzheimer's is enhanced by SPYTACs, a new eTPD platform, offering a safer alternative to anti-Aβ immunotherapy. PMID:41785850, Cell 2026, @Cell www.cell.com/cell/fulltext/S0092-8674... #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

The ubiquitin ligase KLHL6 drives resistance to CD8+ T cell dysfunction | Nature The multifaceted dysfunction of tumour-infiltrating T cells, including exhaustion and mitochondrial dysfunction, remains a major obstacle in cancer immunotherapy1–6. Transcriptomic and epigenomic regulation of T cell dysfunction have been extensively studied7–9, but the role of proteostasis in regulating these obstacles remains less defined. Here we combined computational analyses of atlases of T cell exhaustion and mitochondrial fitness with performed targeted in vivo CRISPR screens, which identified the E3 ubiquitin ligase KLHL6 as a dual-negative regulator of both T cell exhaustion and mitochondrial dysfunction. Mechanistically, KLHL6 expression promoted TOX poly-ubiquitination and subsequent proteasomal degradation, thereby attenuating the transition of progenitor exhausted T cells towards terminal exhaustion. Simultaneously, KLHL6 maintained mitochondrial fitness by constraining the excessive mitochondrial fission that occurs during chronic T cell receptor stimulation by means of

KLHL6's role as a ubiquitin ligase complicates T cell dysfunction, contributing to cancer therapy resistance, impacting CD8+ infiltrates. PMID:41535474, Nature 2026, @Nature @OTSociety @NAR_Open https://doi.org/10.1038/s41586-025-09926-8 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Cardiac resynchronization therapy enhances heart failure outcomes with LVEF ≤50%, utilizing biventricular pacing and wide QRS. Tested in 10k+ patients! PMID:41564398, N Engl J Med 2026, @NEJM https://doi.org/10.1056/NEJMra2415650 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Study tested LLMs as medical assistants with 1,298 participants across 10 scenarios. Can LLMs match real-world needs? 🤔💡 PMID:41663592, Nat Med 2026, @NatureMedicine https://doi.org/10.1038/s41591-025-04074-y #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Mammalian digit tips regrow due to soft ECM with hyaluronic acid. Stiff ECM with dense collagen hinders regeneration. Fascinating tissue mechanics! PMID:41955369, Science 2026, @ScienceMagazine https://doi.org/10.1126/science.ady3136 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

PAN2 deletion in mice halts spermiogenesis at step 8/9, causing infertility. Key: mRNA poly(A) tail regulation crucial for male germline development. 🔬👨‍🔬 PMID:41714623, Nat Commun 2026, @NatureComms https://doi.org/10.1038/s41467-026-69639-y #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

NLRP3 inflammasome increases sharply in AIS; impacts EVT. PMID:41923625, Cell Rep Med 2026 www.cell.com/cell-reports-medicine/fu... #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Nucleotide-resolution mapping of regulatory elements via allelic readout of tiled base editing | Nature Communications CRISPR tiling screens have enabled the characterization of regulatory sequences but are limited by low resolution arising from the indirect readout of editing via guide RNA sequencing and enrichment analysis. This study introduces an end-to-end experimental assay and computational pipeline, which leverages targeted sequencing of CRISPR-introduced alleles at the endogenous target locus following dense base-editing mutagenesis. As a proof of concept, we studied a putative CD19 enhancer, an immunotherapy target in leukemia, and identified alleles and single nucleotides crucial for CD19 regulation. Our visualization tools revealed transcription factor motifs corresponding to the top-ranked nucleotides. Validation experiments confirmed that mutations in MYB, PAX5, and EBF1 binding sites reduce CD19 expression. Critically, editing MYB and PAX5 motifs conferred resistance to CD19 CAR-T cell therapy, revealing how non-coding variants can drive immunotherapy escape. Taken together, this approac

New study unveils a nucleotide-resolution methodology for mapping regulatory elements, using CRISPR base-editing on CD19 enhancer. PMID:41771871, Nat Commun 2026, @NatureComms @OTSociety @NAR_Open https://doi.org/10.1038/s41467-026-69918-8 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Mechanism of co-transcriptional cap snatching by influenza polymerase | Nature Influenza virus mRNAs are stable and competent for nuclear export and translation because they receive a 5′ cap(1) structure in a process called cap snatching1. During cap snatching, the viral RNA-dependent RNA polymerase (FluPol) binds to host RNA polymerase II (Pol II) and the emerging transcript2,3. The FluPol endonuclease then cleaves a capped RNA fragment that subsequently acts as a primer for the transcription of viral genes4,5. Here we present the cryogenic electron microscopy structure of FluPol bound to a transcribing Pol II in complex with the elongation factor DSIF in the pre-cleavage state. The structure shows that FluPol directly interacts with both Pol II and DSIF, positioning the FluPol endonuclease domain near the RNA exit channel of Pol II. These interactions are important for the endonuclease activity of FluPol and FluPol activity in cells. A second structure, trapped after cap snatching, shows that the cleaved capped RNA rearranges within FluPol, directing the c

Discover the co-transcriptional cap snatching by influenza virus polymerase: Cryo-EM reveals how FluPol hijacks Pol II to prime viral gene transcription. PMID:41781612, Nature 2026, @Nature https://doi.org/10.1038/s41586-026-10189-0 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Discover the budding yeast telomerase structure via cryo-EM: RNA TLC1, Est1, Est2, Est3, and Pop1/6/7 form its unique core. Fascinating! PMID:41886584, Science 2026, @ScienceMagazine https://doi.org/10.1126/science.adz5344 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Explore the distinct roles of alternative promoters in drug response using CRISPRi screens, revealing functions in 60% of genes. PMID:41728950, Nucleic Acids Res 2026, @NAR_Open @OTSociety @NAR_Open https://doi.org/10.1093/nar/gkag118 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Personalized brain decoding of spontaneous pain in individuals with chronic pain | Nature Neuroscience Spontaneous pain is a hallmark of chronic pain disorders, but its assessment remains limited by the lack of objective biomarkers. Here we used precision functional magnetic resonance imaging data, collected over more than half a year from two individuals with chronic pain, to develop personalized brain-decoding models of spontaneous pain. The personalized decoding models accurately tracked fluctuations in spontaneous pain intensity across sessions, runs and minutes (Participant 1: prediction–outcome correlation, r = 0.40–0.61; Participant 2: r = 0.51–0.65) and effectively discriminated between median-dichotomized high- versus low-pain states (Participant 1: area under the curve = 0.71–0.87; Participant 2: area under the curve = 0.76–0.93). Model performance improved with increased training data, with conventional data quantities failing to achieve significant predictive accuracy. Furthermore, each model relied on individually unique brain features and did not generalize across particip

Study uses fMRI data from 2 chronic pain patients over 6+ months to develop personalized brain models that reliably predict pain intensity variations. PMID:41748786, Nat Neurosci 2026, @NatureNeuro https://doi.org/10.1038/s41593-026-02221-3 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪